[(18)F]FDG-6-P as a novel in vivo tool for imaging staphylococcal infections.
[(18)F]FDG-6-P as a novel in vivo tool for imaging staphylococcal infections.
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DOI：
10.1186/s13550-015-0095-1
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发表时间：
2015
期刊：
影响因子：
3.2
通讯作者：
Hill PJ
中科院分区：
文献类型：
--
作者：
Mills B;Awais RO;Luckett J;Turton D;Williams P;Perkins AC;Hill PJ
感染的管理是一个主要的临床问题。金黄色葡萄球菌是一种革兰氏阳性细菌，大约三分之一的成年人都有这种细菌。葡萄球菌感染可危及生命，并经常并发多重抗生素耐药菌株，包括耐甲氧西林金黄色葡萄球菌（MRSA）。氟脱氧葡萄糖（[18F]FDG）成像已被用于识别感染部位；然而，它无法区分无菌炎症和细菌负荷。我们通过磷酸化修饰[18F]FDG，产生[18F]FDG-6- p，以促进金黄色葡萄球菌通过己糖磷酸转运体特异性摄取和积累，而己糖磷酸转运体不存在于哺乳动物细胞膜中。这种方法导致放射性药物被细菌特异性吸收，而不是无菌炎症部位。由[18F]FDG合成[18F]FDG-6- p。采用反相高效液相色谱法和薄层色谱法对产物的收率、纯度和稳定性进行了验证。[18F]FDG-6-P对细菌通用己糖磷酸转运体（universal hexose phosphate transporter， UHPT）的特异性通过体外金黄色葡萄球菌和哺乳动物细胞实验得到证实。在小鼠异物感染模型中建立了[18F]FDG-6-P在生物发光葡萄球菌感染部位的全身生物分布和蓄积。体外验证实验表明[18F]FDG-6-P是稳定的，可以特异性地转运到金黄色葡萄球菌中，但不能转运到哺乳动物细胞中。[18F]与未感染的对照组相比，体内金黄色葡萄球菌感染部位的FDG-6-P升高；然而，信号的增加并不显著，出乎意料的是，[18F]FDG-6- p的全身生物分布与[18F]FDG相似。尽管有结论性的体外验证，[18F]FDG-6-P在体内的表现并不像预测的那样。然而，在已知感染部位，[18F]FDG-6-P水平与未感染的对照组相比升高，提供更高的信噪比。细菌UHPT可以运输葡萄糖以外的己糖磷酸盐，因此替代糖可能表现出不同的生物分布，并为特定的细菌检测提供了一种手段。
Management of infection is a major clinical problem. Staphylococcus aureus is a Gram-positive bacterium which colonises approximately one third of the adult human population. Staphylococcal infections can be life-threatening and are frequently complicated by multi-antibiotic resistant strains including methicillin-resistant S. aureus (MRSA). Fluorodeoxyglucose ([18F]FDG) imaging has been used to identify infection sites; however, it is unable to distinguish between sterile inflammation and bacterial load. We have modified [18F]FDG by phosphorylation, producing [18F]FDG-6-P to facilitate specific uptake and accumulation by S. aureus through hexose phosphate transporters, which are not present in mammalian cell membranes. This approach leads to the specific uptake of the radiopharmaceutical into the bacteria and not the sites of sterile inflammation. [18F]FDG-6-P was synthesised from [18F]FDG. Yield, purity and stability were confirmed by RP-HPLC and iTLC. The specificity of [18F]FDG-6-P for the bacterial universal hexose phosphate transporter (UHPT) was confirmed with S. aureus and mammalian cell assays in vitro. Whole body biodistribution and accumulation of [18F]FDG-6-P at the sites of bioluminescent staphylococcal infection were established in a murine foreign body infection model. In vitro validation assays demonstrated that [18F]FDG-6-P was stable and specifically transported into S. aureus but not mammalian cells. [18F]FDG-6-P was elevated at the sites of S. aureus infection in vivo compared to uninfected controls; however, the increase in signal was not significant and unexpectedly, the whole-body biodistribution of [18F]FDG-6-P was similar to that of [18F]FDG. Despite conclusive in vitro validation, [18F]FDG-6-P did not behave as predicted in vivo. However at the site of known infection, [18F]FDG-6-P levels were elevated compared with uninfected controls, providing a higher signal-to-noise ratio. The bacterial UHPT can transport hexose phosphates other than glucose, and therefore alternative sugars may show differential biodistribution and provide a means for specific bacterial detection.
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影响因子：
46.9
作者：
通讯作者：
--
影响因子：
14.2
作者：
Kluytmans-VandenBergh, MFQ;Kluytmans, JAJW
通讯作者：
Kluytmans, JAJW
DOI：
10.1007/s00259-013-2597-2
发表时间：
2014-03-01
影响因子：
9.1
作者：
Aksoy, Sabire Yilmaz;Asa, Sertac;Kanmaz, Bedii
通讯作者：
Kanmaz, Bedii
影响因子：
3.7
作者：
Gowrishankar G;Namavari M;Jouannot EB;Hoehne A;Reeves R;Hardy J;Gambhir SS
通讯作者：
Gambhir SS
影响因子：
1.3
作者：
Kim, Chulhan;Kim, In Hye;Kim, Seok-ki
通讯作者：
Kim, Seok-ki